Human natural killer (NK) cells, monocytes, and dendritic cells are important components of the innate immune functions with instant protections against cancer cells and infections. Monocytes are large white blood cells (also called leukocytes). They can become macrophages and obtain some properties of dendritic cells. Dendritic cells (DCs) are antigen-presenting cells that may perform as messengers between the innate and adaptive immunity. B and T lymphocytes are important for the adaptive immunity with previous sensitization for activation and prolonged defense.

NK cells are cytotoxic and especially powerful for anti-cancer and anti-microbial functions. The cytotoxicity of NK cells can be triggered by the overall effects of stimulating and inhibitory signals released from surface receptors. Activating signals may come from stress-stimulated ligands and pathogenic molecules (Poupot et al., 2016).

The proliferation of the NK cells may depend on the activation of monocytes. Complicated interactions are involved in the associations between monocytes/macrophages and NK cells. Studies have found that amino-bis(methylene phosphonate)-capped PPH dendrimers may activate monocytes and stimulate the proliferation of NK cells with the direct cellular contacts between the two types of cells (Poupot et al., 2016).

Dendrimer-activated monocytes may generate a positive signal for the proliferation of NK cells. However, NK cells may kill the dendrimer-activated monocytes for amplification, especially when monocytes are involved in the anti-inflammatory pathway (Poupot et al., 2016). It is necessary to consider such complex interactions when using poly(phosphorhydrazone) dendrimers for NK-cell based anti-cancer treatments.

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